Although the use of synthetic polymers in technology and in everyday life is widespread, the use of polymers in clinical and laboratory medicine has been cautious and limited. This restricted use is unrelated to need; suitable synthetic polymers are increasingly in demand for use in the fabrication of artificial organs and membranes for hemodialysis or oxygenation, in the preparation of plasma or blood substitutes, and in the manufacture of implanted or soluble polymers as substrates for the slow release of drugs, hormones or other physiologically-active agents.
Unfortunately, even those synthetic polymers which demonstrate relatively low cytotoxicity, such as the various silicone resins, typically demonstrate at least some degree of bioincompatibility. For example, a silicone resin implant embedded within mammalian or human tissue ordinarily eventuates encapsulation of that implant, including epithelial encapsulation or thickening and/or keratinization of the surrounding connective tissues. A similar phenomenon in vitro prevents cells from adhering to many synthetic polymer substrates when those substrates are subjected to elongation or other stresses.
With respect to in vitro cell cultures, specifically, there is as great a need for elastomeric substrates to which cells can adhere in vitro as there is a need for biocompatible polymers for in vivo applications. This need arose from developments in the area of in vitro flexing of cell cultures, which flexing techniques offer certain advantages over conventional cell culture methods.
Conventional culture plates or bottles used for the propogation of cells in vitro are typically manufactured from polystyrene or glass. The routine method for culturing cells includes inoculating the cells into flasks, single culture dishes or multi-well plates, adding a nutrient medium and incubating the cells under controlled conditions. Alternative methods for the in vitro culturing of cells include growing cells in continuously rolling glass or plastic bottles, so that the cells adhere to the wall of a culture vessel beneath continually rotated medium (cells may alternately be grown in fluted roller bottles that have increased inside surface area), or culturing cells on glass or complex polysaccharide beads, tissue segments or in suspension in a suitable culture medium. With all these methods, however, the culture medium does not exert any deforming stress upon the cells themselves such as would simulate the in vivo stresses applied by tendons, for example, or the cyclic stresses exerted by the heart or lungs on their constituent cells.
To simulate what cells experience in the way of physical deformation in the environment of the lung, cells can be adhered to and grown upon an elastomeric substrate which is cyclically stretched to 20 percent elongation, fifteen times a minute, in order to simulate a resting situation. Lung cells may also be cyclically stretched at 20 percent elongation, 40 times a minute, to simulate an exercise period. Such research may be tailored to address such questions as whether cells are more susceptible to viral infection when they are cyclically stretched or at rest, or whether macrophages phagocytose bacteria more readily if they are subjected to cyclic deformation, and related questions. The answers to these questions can then be considered in the development of treatment plans for patients having viral or bacterial infections.
One system for the in vitro flexing of cells in culture is documented in Banes, A. J. et al., "A New Vacuum-Operated Stress-Providing Instrument That Applies Static or Variable Duration Cyclic Tension or Compression to Cells In Vitro," J. cell Sci., 1985. In that published protocol, however, physical limitations of the plastic (polystyrene) Petri dish precluded more than a limited amount of cyclic deformation in the cell substrate (Petri dish base). (Related in vitro systems are documented in Somjen, D. et al., "Bone Remodeling Induced by Physical Stress in Prostaglandin E.sub.2 Mediated," Biochimica et Biophysica Acta, 627 (1980) 91-100; Leung, D. Y. M. et al., "A New In Vitro System for Studying Cell Response to Mechanical Stimulation," Experimental Cell Research, 109 (1977) 285-298; Leung, D. Y. M. et al., "Cyclic Stretching Stimulates Synthesis of Matrix Components by Arterial Smooth Muscle Cells In Vitro," Science, 191 (1976) 475-477; Hasagawa et al. "Mechanical Stretching Increases the Number of Cultured Bone Cells Synthesizing DNA and Alters Their Pattern of Protein Synthesis," Calcif Tissue Int, 37 (1985) 431-436; and Brunette, D. M. et al., "Mechanical Stretching Increases the Number of Epithelial Cells Synthesizing DNA in Culture," J. Cell Sci, 69 (1984) 35-45.
In view of all of the above, a need remains for a low cytotoxicity synthetic polymer composition which does not promote encapsulation in vivo or cellular nonadherence in vitro. Ideally, such a composition would also offer the various benefits of the silicone resin compositions which are generally known to demonstrate both low cytotoxicity and high tensile and flexural strength.